1. Field of the Invention
The present invention relates to a novel proteinase inhibitor having inhibitory activity against Kex2 proteinase family enzymes, a method for producing the proteinase inhibitor, and a gene encoding the inhibitor.
2. Prior Art
Physiologically active peptides and enzyme proteins are produced as an inactive precursor and then processed into an active, mature peptide or protein through processing by a specific proteinase in many cases. At the site of such processing, a paired basic amino acids such as arginine or lysine are found. Kex2 proteinase derived from the yeast Saccharomyces is the first proteinase which has been found as a specific proteinase recognizing this paired basic amino acids in a substrate and cleaving the substrate on the carboxyl terminal side of the pair. Kex2 proteinase is a serine proteinase involved in the processing of a mating factor of yeast. The carboxyl terminal of Kex2 proteinase is penetrating into the Golgi membrane of yeast and this proteinase performs the processing of the .alpha.-factor precursor and killer toxin precursor coming into Golgi bodies to thereby allow them to be secreted as an active from .alpha.-factor and killer toxin.
A large number of serine proteinases having a structure and a specificity similar to those of Kex2 proteinase have also been found in mammals. It has been made clear that they play an important role in the processing of precursor proteins as a Kex2 proteinase family enzyme (Seidah, N. G., et al. (1991) Enzyme, 45: 271-284). Furin, PACE4 and PC5/6 are Kex2 proteinase family enzymes found in almost every tissue and involved in the processing of precursor proteins of growth factors, serum proteinases, receptors, glycosylated viral coat proteins, exotoxins from Pseudomonal aeruginosa, etc. Proteinases such as PC1/3, PC2, PC4 are expressed cell- or tissue-specifically and mainly involved in the processing of neuropeptides and peptide hormones (Hook, V. Y. H. et al., (1994) FASEB J., 8: 1269-1278).
Recently, there have been increased demands for highly safe and yet highly effective medicines and pesticides. Under the circumstances, researches on physiologically active peptides and proteins derived from microorganism and on the utilization of a portion of their structures as a medicine or pesticides have been positively made. Among all, compounds those which inhibit the activities of enzymes functioning at various phases of biological functions, i.e., enzyme inhibitors are used widely as medicines and pesticides. It can be said that most of medicines and pesticides are enzyme inhibitors. With respect to proteinase inhibitors also, a large number of novel peptides and proteins have been found as proteinase inhibitors as a result of search for substances inhibiting various proteinase activities. Further, these proteinase inhibitors per se or portions of their structures have been synthesized and developed as medicines and pesticides.